The program described herein is directed at the total synthesis of a diverse set of natural products which show biological activity as hormonal, antibiotic, and antifungal agents. Also targeted are structural analogs of the natural ionophores and synthetic C2- symmetric macrodiolides for study as ion transport agents and chiral catalysts. The synthetic schemes presented are designed to provide expedient and stereoselective route, to the target molecules in optically pure form. The routes should be amenable to the production of gram quantities of the targets and molecular analogs thereof for biological screening purposes. Specific synthetic objectives included are the erythromycin antibiotic aglycones, erythronolide B (1) and erythronolide A (2); the ionophore antibiotics indanomycin (3) and griseochelin (4); the marine mollusk metabolite pulo'upone (5), a potential bacteriostat; the corticosteroid adrenosterone (6); and the mycotoxin patulin (7). In addition, a set of "semi-natural" ionophore candidates will be synthesized, including diastereomeric analogs of indanomycin and griseochelin. The C2-symmetric macrodiolides 10 leads to 13 will be prepared from the corresponding hydropyran hydroxy acid monomers by dimerization. These synthetic studies will stress the specific extension and application of the synthetic methods and strategies developed in the previous grant period. Intramolecular cycloaddition and cycloreversion processes, (3.3)-sigmatropic rearrangements for heterocycle synthesis, and the elaboration and fragmentation of heterocycle templates rich in stereochemistry are recurring themes. Acyclic stereocontrol via olefin hydroboration and osmylation will be scrutinized, as will chelation-controlled coupling of nucleophile/electrophile pairs.